Description of Invention: Cell surface biomolecules such as integrins (alphavbeta3, alphavbeta5, alphavbeta8, alpha6beta4), folate receptors, and CD13 are highly expressed in cancer cells and are involved in angiogenesis, invasion and metastasis. Consequently, this has made these cellular biomolecules attractive targets for delivery of drugs that can bind to them selectively. The peptide motifs RGD (Arg-Gly-Asp) and NGR (Asn-Gly-Arg), in particular, are recognized by integrins alphavbeta3 and alphavbeta5 and CD13 with high affinity. Further, short peptide sequences of RGD and NGR are commercially useful because they are amenable to large scale synthesis, chemical modification and are non-immunogenic. Therefore, there is a need for cyclic compounds having the NGR peptide motif to target CD13 or having the RGD peptide motif to target alphavbeta3 and alphavbeta5 integrins.
Accordingly, the researchers at the NIH have developed cyclic NGR and RGD pentapeptide analogs efficiently synthesized on resin via click chemistry. These cyclic peptides are potentially useful in targeted delivery of drugs, antibodies, or nanoparticles to the site of angiogenic blood vessels and tumors. By allowing for targeted drug delivery, these peptides can minimize general cytotoxicity and improve bioavailability. The cyclic peptides described are novel, synthetic analogs of RGD and NGR cyclic peptides. Therefore, their inherent cyclic structure and the cyclization strategy will make these compounds stable from hydrolytic degradation, thereby prolonging their half life in circulation.
Applications: Targeted drug delivery and medical imaging of cancer tissues expressing CD13 or alphavbeta3 and alphavbeta5 integrins.
Advantages:
These cyclic peptides contain a triazole unit that would be less likely to be attacked by hydrolytic enzymes and esterases, thus making them ideal candidates for in vivo targeted delivery and imaging.
The RGD and NGR cyclic peptides are amenable to large scale synthesis, chemical modification and are non-immunogenic, while the linear RGD peptide counterparts are prone to protease degradation making them much less stable and limiting their use in in vivo applications.
Both linear and disulfide-bridged cyclic peptides containing the NGR motif have been used to deliver various anti-tumor compounds and viral particles to tumor vessels, with the cyclic versions showing more than a 10 fold higher binding affinity than their linear counterparts.
Development Status: Pre-clinical proof of principle
Inventors: No Inventor Information Available.
Licensing Status: Available for licensing
For Licensing Information Please Contact: Whitney Hastings NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: hastingw@mail.nih.gov Phone: 301-451-7337 Fax: 301-402-0220
Description of Invention:
Cell surface biomolecules such as integrins (alphavbeta3, alphavbeta5, alphavbeta8, alpha6beta4), folate receptors, and CD13 are highly expressed in cancer cells and are involved in angiogenesis, invasion and metastasis. Consequently, this has made these cellular biomolecules attractive targets for delivery of drugs that can bind to them selectively. The peptide motifs RGD (Arg-Gly-Asp) and NGR (Asn-Gly-Arg), in particular, are recognized by integrins alphavbeta3 and alphavbeta5 and CD13 with high affinity. Further, short peptide sequences of RGD and NGR are commercially useful because they are amenable to large scale synthesis, chemical modification and are non-immunogenic. Therefore, there is a need for cyclic compounds having the NGR peptide motif to target CD13 or having the RGD peptide motif to target alphavbeta3 and alphavbeta5 integrins.
Accordingly, the researchers at the NIH have developed cyclic NGR and RGD pentapeptide analogs efficiently synthesized on resin via click chemistry. These cyclic peptides are potentially useful in targeted delivery of drugs, antibodies, or nanoparticles to the site of angiogenic blood vessels and tumors. By allowing for targeted drug delivery, these peptides can minimize general cytotoxicity and improve bioavailability. The cyclic peptides described are novel, synthetic analogs of RGD and NGR cyclic peptides. Therefore, their inherent cyclic structure and the cyclization strategy will make these compounds stable from hydrolytic degradation, thereby prolonging their half life in circulation.
Applications:
Targeted drug delivery and medical imaging of cancer tissues expressing CD13 or alphavbeta3 and alphavbeta5 integrins.
Advantages:
Development Status:
Pre-clinical proof of principle
Inventors:
No Inventor Information Available.
Licensing Status:
Available for licensing
For Licensing Information Please Contact:
Whitney Hastings
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: hastingw@mail.nih.gov
Phone: 301-451-7337
Fax: 301-402-0220
Ref No: 2195
Updated: 11/2010